Molecular dynamics and free energy simulation methodologies are employed to investigate the conformational ensemble of small peptide systems in vacuo and in solution. One of the major limitations in current simulation methods is the conformational sampling problem. Qualitatively this represents the difficulty in sampling all of the relevant conformational and energetic states of a molecule. The focus is this project is to develop the tools and methodology to allow generation of a conformational ensemble of a small peptide in vacuo and in solution, with the goal of generating the thermodynamic ensemble. An additional problem is properly representing the energetics of the molecule, particularly the long range electrostatic interactions. Working with Tom Darden at the National Institute of Environmental Health Sciences and Michael Crowley of the Pittsburg Supercomputing Center, we are developing and applying the Particle Mesh Ewald method to more accurately represent the energetics. In addition, we are involved in parallelizing and optimizing AMBER for shared memory and distributed memory computers. This allows us to extend the simulation realm from the picosecond to nanosecond range. MidasPlus is used extensively in this work as a visualization tool and the CGL computers are occasionally utilized to test and develop AMBER.